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Biomedical subjects

M D Kendall

Publications and source records attributed to M D Kendall.

At least 37 records · Page 2Linked to original sources
PubMed1994

Involution of the rat thymus in experimentally induced hypothyroidism.

The thymus, as part of the immune-neuroendocrine axis, is greatly influenced by factors from most endocrine glands, especially the thyroid. Antithyroid drugs (carbimazole and methimazole) were used to induce hypothyroidism in rats. Histological and ultrastructural examination of the thymus showed progressive thymic involution after 4 weeks of drug treatment to the end of observations (7 weeks). The involution was characterised by increased thymocyte apoptosis and thymocyte phagocytosis by macrophages. This resulted in thymocyte depopulation, increases in numbers of interdigitating cells, alterations to mainly subcapsular and medullary epithelial cells, an apparent increase of mast cells and collagen in the capsule and septa, and increased numbers of B cells and plasma cells. Lymphoid cells immuno-reactive with MRC OX12 (which detects B cells) were observed within blood vessel walls, suggesting that they may have been moving in and out of the thymus. The administration of drugs causing hypothyroidism, therefore, also caused marked involution of the thymus.

Animals↗
PubMed1994

The effects of pregnancy on the mouse thymic epithelium.

Changes in the murine thymus during pregnancy were studied using immunocytochemistry with monoclonal antibodies against thymic epithelial, neuroendocrine, and thymulin-producing cells, fibroblasts, blood vessels and connective tissue components. Extensive alterations occur in mid-pregnancy. The medulla was greatly enlarged in the involuted thymus, and there were greater numbers of epithelial cells. These epithelial cells had an altered distribution forming large structures surrounding spherical masses of mononuclear cells, lacked epithelial cells and often contained a central blood vessel with fibroblasts and connective tissue. We have called these structures 'medullary epithelial rings' (MERs). To our knowledge these structures have not been described before. Late in pregnancy the loss of the central mononuclear cells leaves collapsed structures in a smaller medulla that nevertheless retains many epithelial cells. In virgins and early-pregnancy, there are cortical channels free of epithelial cells that are very infrequent later in pregnancy. This may reflect the loss of steroid-sensitive thymocytes from the cortex. The influence of sex-steroids, neurological impulses and immune activity in causing the changes are discussed, as are the possible consequences in pregnancy of a reduced, thymocyte-depleted cortex and an enlarged medulla that shows great complexity and activity.

Animals↗
PubMed1994

The thymus in pregnancy: the interplay of neural, endocrine and immune influences.

This article discusses the dramatic events that accompany thymic involution during pregnancy, and traces the possible immune, neural and endocrine interactions that may occur. Ann Clarke and Marion Kendall present accumulating evidence that activity, not inactivity, is a feature of the thymus at this time. Whilst the cortex shrinks, the medulla enlarges and rearranges to create a microenvironment containing increased numbers of mature thymocytes. It is suggested that these recently derived T cells may contribute to the unique populations of cells with suppressive function that appear during pregnancy, and thereby contribute to the immune suppression of the mother to paternal and fetal antigens. In addition, the pregnancy-associated cortical involution of the thymus may reflect the deletion of clones with potential reactivity to paternal and/or fetal antigens.

Animals↗
PubMed1994

The noradrenergic innervation of the rat thymus during pregnancy and in the post partum period.

The noradrenergic innervation of the rat thymus during pregnancy and the post partum period was examined by a sucrose glyoxylic acid method for catecholamines, and by high pressure liquid chromatography. Fluorescent nerves decreased in number throughout pregnancy when there was an overall loss in thymic weight due to cortical involution. These changes are maximal by parturition. There was a dramatic increase in nerves between d 21 of pregnancy and d 1 after parturition, especially in the capsule and around blood vessels in the connective tissue septa. The neonates were removed at parturition and thymic weight was rapidly regained. The increased numbers of nerves remained throughout this post partum period. Noradrenaline levels in the thymus altered in a similar pattern throughout pregnancy and the post partum period, but did not parallel thymic weight changes. The mean noradrenaline concentration in the virgin thymus was 1063 +/- 107 pg/mg protein. Levels remained similar during early pregnancy and increased significantly at d 16. Virgin levels were regained by d 21. Values peaked after parturition but rapidly decreased over the next 3 days, and remained at or below virgin levels to d 28 except for a transient rise at d 10 post partum. Adrenaline values were consistently below detection levels. This study shows that there are variations in both nerves visualised, and in neurotransmitter (noradrenaline) content in the thymus during the course of pregnancy and the post partum period. Thus thymic function could be influenced by central events (levels of catecholamines in peripheral blood) as well as local events mediated by transmitter changes in nerves.

Animals↗
PubMed1992

Plasma thymulin concentrations, the thymus and organochlorine contaminant levels in seals infected with phocine distemper virus.

Blood samples collected from live common seals (Phoca vitulina) and grey seals (Halichoerus grypus) around the coast of Scotland and Northern Ireland during, and immediately after, an epizootic caused by phocid distemper virus (PDV) were analysed for thymulin content. Thymulin levels were compared with neutralization titres and concentrations of organochlorine contaminants (DDT and its metabolites, seven chlorinated biphenyl congeners) derived from blood and blubber samples collected from the same animals and analysed independently. Thymulin levels in grey seals (mean 2827 +/- 1355 fg/ml) were negatively correlated with the logarithm of virus neutralization titre. In common seals they varied significantly between age classes. There was no direct relationship between thymulin levels and contaminant levels in either species. However, when an estimate of time since exposure was included in the regression analysis for common seals, there was a highly significant relationship between thymulin and the two chlorinated biphenyl congeners with the highest concentrations in blubber.

Adipose Tissue↗
PubMed1992

The thymus: new views of an old gland.

The existence of the thymus was recognised by ancient scientists and doctors, although its vital role in the development and maintenance of the competent T cell repertoire has been fully appreciated only comparatively recently. Current research is now moving on to explore the role of the thymus in interactions between the brain, the nervous system and the immune response. This is an exciting new field which should lead to advances in the management, treatment and prognosis of disease in man and animals.

Receptors, Antigen, T-Cell↗
PubMed1992

Thymulin and its role in immunomodulation.

Even though thymulin was isolated, sequenced and characterised some 20 years ago and later identified as a thymic hormone involved in immunomodulation, much more work is still required to further understanding of the mechanisms of action(s) of this peptide. Since the observation, by a semiquantitative bioassay, of diminished levels of thymulin in immunodeficiency and autoimmune disease, new data obtained by radioimmunoassay have not only confirmed previous observations but also demonstrated that thymulin plays a role in the interaction between the immune system and the neuro-endocrine system. In this paper we give an up to date account of recent developments in research into the role of thymulin in immunomodulation.

Amino Acid Sequence↗
PubMed1991

Innervation of the rat thymus gland.

Current views from different laboratories on the innervation of the thymus gland are reviewed with particular reference to the rat. Noradrenergic nerve profiles of the sympathetic nervous system have been demonstrated in the subcapsular cortex, at the corticomedullary junction and in the cortex itself, and extremely sparsely in the medulla. By following beta-adrenergic receptor development in postnatal rats, it has been shown that there is a marked increase in density and morphological organization of the receptor in the medulla with the maturation of thymocyte function (monitored by measuring the proliferation response to concanavalin A) and a sexual dimorphism during the ontogeny of the receptor. Chemical sympathectomy of adult rats with 6-hydroxydopamine (6-OHDA) or guanethidine resulted in a loss of thymus weight, decreased cellularity, and increased apoptosis but a rise in the numbers of proliferating cells in the cortex. By contrast, proliferation of peripheral T cells was reduced after the use of 6-OHDA. Chemical sympathectomy also demonstrated that there were at least three nerve nets in the gland: noradrenergic neural profiles that were destroyed with both 6-OHDA and guanethidine, vasoactive intestinal polypeptide (VIP)-positive profiles that persisted, and AChE- and CGRP-positive profiles and cells that also persisted but had a different distribution to VIP-positive fibers. Some functional correlates of thymic innervation are discussed although the subject now needs to be further researched.

Acetylcholine↗
PubMed1991

Cell degeneration in alopecia areata. An ultrastructural study.

The morphology and prevalence of different forms of cell degeneration in hair follicles in acute alopecia areata were investigated. In addition to apoptosis and necrosis, a third morphological pattern of cell degeneration, dark-cell transformation, was evident. Fifteen patients with untreated acute alopecia areata and three normal adults without hair loss were studied. Electron microscopy revealed that although apoptosis of outer root sheath keratinocytes produces normal hair follicle involution (catagen), increased levels of apoptosis, necrosis, and dark-cell formation appear to be related to the pathology of alopecia areata. Although cell degeneration was generally restricted to keratinocytes of the lower follicle, melanocytes, Langerhans' and dermal papilla cells were also affected. Keratinocytic degeneration may affect layers of matrix cells in alopecia areata, unlike the apoptosis of scattered outer root sheath cells in normal catagen. The extent of cell death suggests a pathological rather than a physiological event in alopecia areata.

Acute Disease↗
PubMed1991

Functional anatomy of the thymic microenvironment.

This paper presents a review of our current understanding of the nature of the thymic microenvironment, after briefly considering the major role of the gland. The epithelial cells and their products are of fundamental importance, and other cells of the macrophage series are implicated in most functional events. The embryological origin of the epithelium is still not clear, although disease conditions would suggest a single origin. Immigration and emigration of thymocytes is considered, and also the passage of antigens into the gland. The events within the thymus are under the control of the CNS acting through the innervation or via hormonal pathways. Both of these areas are considered in detail, especially thymic hormone origins, functions and interactions.

Animals↗
PubMed1991

Effect of a platinum chemotherapy drug on intracellular elements during the cell cycle, using X-ray microanalysis.

Intracellular elemental concentrations were measured in the cytoplasm, nucleus and nucleolus of cultured Chinese hamster ovary (CHO) cells, using energy dispersive electron probe X-ray microanalysis and transmission electron microscopy. Synchronous CHO cell populations were analyzed at different times during the growth cycle. The elements K, P, Mg and Zn were all more concentrated in the nucleus and nucleolus than in the cytoplasm, while no specific subcellular compartmentalization was evident for the elements Na, Cl, Ca, Fe and S. Significant changes in intracellular elemental concentrations were associated with the progression of cells from G1 phase to S phase of the growth cycle. Most significant were the effects on the monovalent ions, Na, K and Cl. The effect of a second generation platinum chemotherapy agent, cis-dichloro-bis (isopropylamine) trans-dihydroxy platinum IV (iproplatin) on intracellular elements was investigated by analyzing subcellular compartments of drug-treated synchronous CHO cell populations. Changes in intracellular elemental levels occurred, most notably in the nucleus of G1 phase cells, when a general depletion of most essential elements was evident. Attempts to analyze cells for their Pt content proved disappointing, since quantitation for Pt was not possible. However, measurement of Pt peak/background ratio yielded significant Pt peaks on analyzing lysosomes of cells treated with high concentrations of iproplatin. These Pt peaks were associated with high levels of S and Fe.

Animals↗
PubMed1991

Identification of neural profiles containing vasoactive intestinal polypeptide, acetylcholinesterase and catecholamines in the rat thymus.

Sympathetic and parasympathetic innervation of the rat thymus is described using immunohistochemical, fluorescence histochemical and histochemical methods. Sympathetic innervation was found to enter the gland with the vasculature and to be distributed mainly in the subcapsular and corticomedullary junctional areas of the cortex. The parasympathetic innervation was also found to enter the gland with the vasculature, but was distributed to both cortex and medulla. Acetylcholinesterase-positive staining cells were seen in the medulla. Ideas about the function of thymus innervation are discussed.

Acetylcholinesterase↗
PubMed1990

A new radioimmunoassay for the thymic peptide thymulin, and its application for measuring thymulin in blood samples.

A new, specific and sensitive radioimmunoassay, using a polyclonal antiserum raised in rabbits, is described for quantitating plasma thymulin. As little as 300 fg thymulin can be measured in one assay tube. The method has been used to measure thymulin in human blood (umbilical vessel blood, 2191 +/- 123 fg/ml; children and adults up to the age of 20 years, 1499 +/- 119 fg/ml; and adults between 21-65 years, 371 +/- 18 fg/ml). There is a highly significant decrease within these three groups (P less than 0.001 by one way analysis of variance). Also plasma thymulin levels were determined in rats (601 +/- 127 fg/ml) and in pooled plasma samples from mice (638 +/- 56 fg/ml). No thymulin was detected in plasma obtained from nude rats, nude mice and thymectomised mice. These results show that the radioimmunoassay described here is a useful quantitative tool for measuring plasma thymulin that will have applications in basic, applied and clinical research.

Animals↗
PubMed1990

Reversal of ageing changes in the thymus of rats by chemical or surgical castration.

Differences in the thymus of young and old male CSE Wistar rats were examined by use of routine histological stains on paraffin-embedded sections. There was a highly significant loss of thymic weight and disruption of architecture with age. Both surgical castration and chemical castration induced by a luteinizing hormone-releasing hormone analogue (Goserelin) caused a significant increase in thymic weight and the reappearance of a well-defined cortex and medulla in ageing rats. Cell surface antigens were detected on cryosections after incubation with a range of monoclonal antibodies. The Pan T cell marker (detected with antibody W3/13) showed fewer positive cells in ageing rats, and an increase after chemical castration. The smaller glands of old rats had fewer positive T cells with CD4 (MRC OX35) and CD8 (MRC OX8) antigens, and more after chemical castration in both young and ageing rats, but the greatest changes were seen in the intensity of Class II major histocompatibility complex (MRC OX6) immunoreactivity. In both young and ageing chemically-castrated rats, the number of cells and the intensity of immunoreactivity were greatly increased in the medulla.

Aging↗
PubMed1990

Ultrastructural observations on the hair bulb melanocytes and melanosomes in acute alopecia areata.

It is well recognized that alopecia areata (Aa) may preferentially affect pigmented hair and may spare white hair, and that regrowing hair in the disease is often initially white. In addition, there is an association with vitiligo and ocular depigmentation. To date, the pathomechanisms of the melanocyte effects are unclear. We have studied 10 patients with untreated acute alopecia areata, and three normal patients without hair loss. Morphologic changes, studied by conventional light and electron microscopy, in the cytoplasm of affected melanocytes often predated nuclear hyperchromatism. Increased numbers of bizarre melanosomes were found in affected melanocytes compared with normal ones; such melanosomes had incomplete or "aborted" melanization, resulting in poor pigment deposition, and were disrupted, enlarged and rounded, with loss of normal ellipsoidal shape. An unusual outer root sheath (ORS) distribution of hair bulb melanocytes was seen. Other atypical melanosome effects included marked pigment displacement into peribulbar and DP melanophages. In the DP clumped melanin granules formed giant spherical complexes without discernible limiting membranes, which were sometimes associated with lymphocytes. These morphologic changes indicate an active involvement of hair bulb melanocytes in alopecia areata.

Acute Disease↗
PubMed1990

Ultrastructural study of exclamation-mark hair shafts in alopecia areata.

The prime diagnostic feature of acute alopecia areata is the presence of exclamation mark hairs. These characteristic hairs fracture at their distal end and taper proximally towards the scalp, giving them the appearance of an exclamation mark. Hair morphology was studied in 8 patients with untreated acute alopecia areata and 3 normal adults without hair loss. Light microscopy, transmission and scanning electron microscopy revealed distinct structural differences in the distal end of hairs compared with the remainder of their length and with normal hair shafts. Transverse sections of hairs just below the frayed brush-like tip often displayed asymmetrical cortex disintegration. One side was compact and homogeneous while the other was deeply fissured and/or broken up into discrete heterogeneous-staining fragments of cortical, stratum corneum and cuticular components in addition to apparently degenerate cortex. Many exclamation mark hair tips lacked cuticle and had irregular profiles. Melanin was found in cortical and medullary fragments at the tip, although it was absent in the more degenerate forms of cortex. More proximal sections of these pathognomic telogen hairs revealed nearly normal hair shaft ultrastructure.

Acute Disease↗